Wang Sen, Wang Lin, Zhao Yu
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Cancers (Basel). 2025 Mar 31;17(7):1184. doi: 10.3390/cancers17071184.
: Radiotherapy is a key treatment for cancer, effectively controlling local tumor growth through DNA damage that induces senescence or apoptosis in cancer cells. However, radiotherapy can trigger complex cellular reactions, such as cell senescence, which is characterized by irreversible cell cycle arrest and the secretion of pro-inflammatory factors known as the senescent-associated secretory phenotype (SASP). : This study investigates the regulatory role of , a key enzyme implicated in cancer cell metabolism and radiotherapy resistance, in the induction of senescence and SASP. Using in vitro models, we demonstrate that knockdown accelerates cellular senescent-like phenotype while regulating the SASP through the cGAS-STING immune response pathway. : Our results indicate that while knockdown promotes senescence, it reduces the secretion of pro-inflammatory factors via inhibition of the cGAS-STING pathway, potentially mitigating SASP-related tumor progression. : These findings provide insights into the molecular mechanisms underlying prostate cancer cell senescence and suggest that could be a potential therapeutic target to enhance the efficacy of radiotherapy while controlling the adverse effects of SASP.
放疗是癌症的关键治疗方法，通过诱导癌细胞衰老或凋亡的DNA损伤有效控制局部肿瘤生长。然而，放疗会引发复杂的细胞反应，如细胞衰老，其特征是不可逆的细胞周期停滞以及被称为衰老相关分泌表型（SASP）的促炎因子分泌。本研究调查了参与癌细胞代谢和放疗抗性的关键酶在衰老诱导和SASP中的调节作用。使用体外模型，我们证明该酶敲低可加速细胞衰老样表型，同时通过cGAS-STING免疫反应途径调节SASP。我们的结果表明，虽然该酶敲低促进衰老，但它通过抑制cGAS-STING途径减少促炎因子的分泌，可能减轻与SASP相关的肿瘤进展。这些发现为前列腺癌细胞衰老的分子机制提供了见解，并表明该酶可能是增强放疗疗效同时控制SASP不良影响的潜在治疗靶点。
